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1.
Oncologist ; 28(11): e1108-e1113, 2023 Nov 02.
Artículo en Inglés | MEDLINE | ID: mdl-37284901

RESUMEN

BACKGROUND: In this phase Ib study MODURATE, we optimized the dosing schedule and tested the efficacy and safety of trifluridine/tipiracil, irinotecan, and bevacizumab in patients with metastatic colorectal cancer with fluoropyrimidine and oxaliplatin treatment failure. METHODS: We included a dose escalation (3 + 3 design) and an expansion cohort. Patients were administered trifluridine/tipiracil (25-35 mg/m2 twice daily, days 1-5), irinotecan (150-180 mg/m2, day 1), and bevacizumab (5 mg/kg, day 1) every 2 weeks. The recommended phase II dose (RP2D) in the dose escalation cohort was administered to at least 15 patients in both cohorts combined. RESULTS: Twenty-eight patients were enrolled. Five dose-limiting toxicities were observed. RP2D was defined as trifluridine/tipiracil 35 mg/m2, irinotecan 150 mg/m2, and bevacizumab 5 mg/kg. Of 16 patients who received RP2D, 86% (14/16) experienced grade ≥3 neutropenia without febrile neutropenia. Dose reduction, delay, and discontinuation occurred in 94%, 94%, and 6% of patients, respectively. Three patients (19%) showed partial response and 5 had stable disease for >4 months, with a median progression-free and overall survival of 7.1 and 21.7 months, respectively. CONCLUSION: Biweekly trifluridine/tipiracil, irinotecan, and bevacizumab administration may have moderate antitumor activity with high risk of severe myelotoxicity in previously treated patients with metastatic colorectal cancer [UMIN Clinical Trials Registry (UMIN000019828) and Japan Registry of Clinical Trials (jRCTs041180028)].


Asunto(s)
Neoplasias del Colon , Neoplasias Colorrectales , Neoplasias del Recto , Humanos , Bevacizumab/uso terapéutico , Irinotecán/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológico , Uracilo , Trifluridina , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias del Colon/tratamiento farmacológico , Neoplasias del Recto/tratamiento farmacológico , Combinación de Medicamentos
2.
Invest New Drugs ; 40(5): 1106-1116, 2022 10.
Artículo en Inglés | MEDLINE | ID: mdl-35900709

RESUMEN

PURPOSE: This study aimed to evaluate the effectiveness and safety of gemcitabine (GEM) plus nab-paclitaxel (GnP) in patients aged ≥ 75 years with advanced pancreatic cancer and compare it with monotherapy (GEM or S-1). METHODS: We retrospectively reviewed the data of consecutive patients with advanced pancreatic cancer aged ≥ 75 years who received either GnP or monotherapy (GEM or S-1) between January 2014 and May 2020. The primary efficacy outcome was overall survival (OS). RESULTS: A total of 96 patients were included in this study; 51 were treated with GnP and 45 with monotherapy (31 with GEM and 14 with S-1). The median OS and progression-free survival were 10.8 and 6.7 months in the GnP group and 10.7 and 4.3 months in the monotherapy group, respectively. The treatment effect on OS was consistently favorable in the GnP group across most subgroups, particularly in patients with locally advanced cancer, modified Glasgow prognostic score of 0 or 1, and neutrophil/lymphocyte ratio < 3.1. The disease control rates were 76% and 48% in the GnP and monotherapy groups, respectively, and grade 3 or 4 neutropenia occurred in 23 (45%) and 11 (24%) patients of the GnP and monotherapy groups, respectively. CONCLUSIONS: This study demonstrated that GnP was not superior to monotherapy with regard to OS. However, multivariate analysis showed that GnP treatment positively affected the OS and could be considered as a treatment option, even for elderly patients.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Pancreáticas , Anciano , Albúminas/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Desoxicitidina/análogos & derivados , Humanos , Paclitaxel/efectos adversos , Neoplasias Pancreáticas/tratamiento farmacológico , Estudios Retrospectivos , Resultado del Tratamiento , Gemcitabina , Neoplasias Pancreáticas
3.
BMC Cancer ; 22(1): 73, 2022 Jan 17.
Artículo en Inglés | MEDLINE | ID: mdl-35039004

RESUMEN

BACKGROUND: Microsatellite instability (MSI) is a key marker for predicting the response of immune checkpoint inhibitors (ICIs) and for screening Lynch syndrome (LS). AIM: This study aimed to see the characteristics of cancers with high level of MSI (MSI-H) in genetic medicine and precision medicine. METHODS: This study analyzed the incidence of MSI-H in 1000 cancers and compared according to several clinical and demographic factors. RESULTS: The incidence of MSI-H was highest in endometrial cancers (26.7%, 20/75), followed by small intestine (20%, 3/15) and colorectal cancers (CRCs)(13.7%, 64/466); the sum of these three cancers (15.6%) was significantly higher than that of other types (2.5%)(P < 0.0001). MSI-H was associated with LS-related cancers (P < 0.0001), younger age (P = 0.009), and family history, but not with smoking, drinking, or serum hepatitis virus markers. In CRC cases, MSI-H was significantly associated with a family history of LS-related cancer (P < 0.0001), Amsterdam II criteria [odds ratio (OR): 5.96], right side CRCs (OR: 4.89), and multiplicity (OR: 3.31). However, MSI-H was very rare in pancreatic (0.6%, 1/162) and biliary cancers (1.6%, 1/64) and was null in 25 familial pancreatic cancers. MSI-H was more recognized in cancers analyzed for genetic counseling (33.3%) than in those for ICI companion diagnostics (3.1%)(P < 0.0001). Even in CRCs, MSI-H was limited to 3.3% when analyzed for drug use. CONCLUSIONS: MSI-H was predominantly recognized in LS-related cancer cases with specific family histories and younger age. MSI-H was limited to a small proportion in precision medicine especially for non-LS-related cancer cases.


Asunto(s)
Neoplasias Colorrectales Hereditarias sin Poliposis/genética , Neoplasias Colorrectales/genética , Anamnesis/estadística & datos numéricos , Inestabilidad de Microsatélites , Neoplasias/genética , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Medicina de Precisión
4.
Jpn J Clin Oncol ; 52(6): 599-608, 2022 May 31.
Artículo en Inglés | MEDLINE | ID: mdl-35411369

RESUMEN

OBJECTIVE: Since 2019, precision cancer medicine has been covered by national insurance in Japan; however, to date, germline findings have not been fully reported. The aim of this study was to evaluate the current status and raise a problem of germline finding analysis and disclosure in Japanese precision cancer medicine. METHODS: Germline findings of 52 genes were examined in 296 cases with advanced cancer by a case series study. RESULTS: Six (2.0%) cases were examined by the Oncoguide™ NCC Oncopanel with germline testing, but no germline findings were reported. The remaining 290 (98.0%) cases were analyzed by FoundationOne® CDx (tumor-only testing), which recognized 404 pathogenic variants; those of BRCA1/2 were recognized in 16 (5.5%) tumors. Our institutional algorithm suggested 39 candidate germline findings in 34 cases, while the public algorithm listed at least 91 candidate germline findings. Four germline findings had been previously identified (BRCA1: 3 and ATM: 1). Nine of 30 cases with candidate germline findings excluding these known germline findings refused or deferred germline testing. Only 4 of 16 cases that received counseling underwent germline testing, and those 4 revealed 3 germline findings (BRCA2, CDK4 and RAD51C); in total, 8 (2.7%) germline findings were revealed. Reasons for refusing genetic counseling and/or germline testing included extra hospital visits, added expense for germline testing due to limited national insurance coverage, poor patient physical condition and no known family members associated with the possible germline finding. CONCLUSIONS: In current Japanese precision cancer medicine, only a small fraction of the patients undergoes germline testing and demonstrated germline finding. The current results suggested a need for earlier indications for precision cancer medicine, broader insurance coverage and more efficient germline finding prediction algorithms, to increase the number of germline testings and to improve the following managements.


Asunto(s)
Neoplasias , Medicina de Precisión , Predisposición Genética a la Enfermedad , Pruebas Genéticas/métodos , Células Germinativas , Mutación de Línea Germinal , Humanos , Japón , Neoplasias/genética , Neoplasias/terapia
5.
Cancer Sci ; 112(7): 2915-2920, 2021 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-33931919

RESUMEN

Adjuvant chemotherapy has reduced the risk of tumor recurrence and improved survival in patients with resected colorectal cancer. Potential utility of circulating tumor DNA (ctDNA) prior to and post surgery has been reported across various solid tumors. We initiated a new type of adaptive platform trials to evaluate the clinical benefits of ctDNA analysis and refine precision adjuvant therapy for resectable colorectal cancer, named CIRCULATE-Japan including three clinical trials. The GALAXY study is a prospectively conducted large-scale registry designed to monitor ctDNA for patients with clinical stage II to IV or recurrent colorectal cancer who can undergo complete surgical resection. The VEGA trial is a randomized phase III study designed to test whether postoperative surgery alone is noninferior to the standard therapy with capecitabine plus oxaliplatin for 3 months in patients with high-risk stage II or low-risk stage III colon cancer if ctDNA status is negative at week 4 after curative surgery in the GALAXY study. The ALTAIR trial is a double-blind, phase III study designed to establish the superiority of trifluridine/tipiracil as compared with placebo in patients with resected colorectal cancer who show circulating tumor-positive status in the GALAXY study. Therefore, CIRCULATE-Japan encompasses both "de-escalation" and "escalation" trials for ctDNA-negative and -positive patients, respectively, and helps to answer whether measuring ctDNA postoperatively has prognostic and/or predictive value. Our ctDNA-guided adaptive platform trials will accelerate clinical development toward further precision oncology in the field of adjuvant therapy. Analysis of ctDNA status could be utilized as a predictor of risk stratification for recurrence and to monitor the effectiveness of adjuvant chemotherapy. ctDNA is a promising, noninvasive tumor biomarker that can aid in tumor monitoring throughout disease management.


Asunto(s)
ADN Tumoral Circulante/sangre , Neoplasias Colorrectales/sangre , Recurrencia Local de Neoplasia/sangre , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Capecitabina/administración & dosificación , Quimioterapia Adyuvante , Neoplasias del Colon/sangre , Neoplasias del Colon/genética , Neoplasias del Colon/patología , Neoplasias del Colon/terapia , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/terapia , Método Doble Ciego , Humanos , Japón , Recurrencia Local de Neoplasia/genética , Recurrencia Local de Neoplasia/patología , Recurrencia Local de Neoplasia/terapia , Oxaliplatino/administración & dosificación , Estudios Prospectivos , Pirrolidinas/administración & dosificación , Timina/administración & dosificación , Trifluridina/administración & dosificación
6.
Oncologist ; 26(10): 845-853, 2021 10.
Artículo en Inglés | MEDLINE | ID: mdl-34232546

RESUMEN

BACKGROUND: KRAS is one of the most frequently mutated oncogenes in colorectal cancer (CRC). Recently, a novel therapy targeting KRAS G12C mutation has demonstrated promising activities for corresponding advanced solid tumors, including metastatic CRC (mCRC). However, the prognostic impact of the KRAS G12C mutation remains unclear in patients with mCRC. MATERIALS AND METHODS: We retrospectively reviewed medical records of patients with mCRC who received first-line chemotherapy between January 2005 and December 2017 at four large oncology facilities in Japan. Survival outcomes were compared between patients with KRAS G12C and those with non-G12C mutations. RESULTS: Among 2,457 patients with mCRC, 1,632 met selection criteria, and of these, 696 had KRAS exon 2 mutations, including 45 with KRAS G12C mutation tumors. Patient characteristics were not significantly different between the KRAS G12C and non-G12C groups. At a median follow-up of 64.8 months, patients with the KRAS G12C mutation showed significantly shorter first-line progression-free survival (PFS; median, 9.4 vs. 10.8 months; p = .015) and overall survival (OS; median, 21.1 vs. 27.3 months; p = .015) than those with non-G12C mutations. Multivariate analysis also showed that KRAS G12C mutation was significantly associated with shorter PFS (hazard ratio [HR], 1.43; 95% confidence interval [CI], 1.04-1.96, p = .030) and OS (HR, 1.42; 95% CI, 1.01-2.00; p = .044). CONCLUSION: We demonstrate that, compared with non-G12C mutations, KRAS G12C mutation is significantly correlated with shorter first-line PFS and OS. These findings indicate the relevance of a stratified treatment targeting KRAS G12C mutation in mCRC. IMPLICATIONS FOR PRACTICE: Among patients with KRAS exon 2 mutated metastatic colorectal cancer (mCRC), median progression-free survival (PFS) and overall survival (OS) were 9.4 and 21.1 months, respectively, for G12C mutation and 10.8 and 27.3 months, respectively, for patients with non-G12C mutations, indicating significantly shorter PFS (hazard ratio [HR], 1.47; 95% confidence interval [CI], 1.08-2.01; p = .015) and OS (HR, 1.50; 95% CI, 1.08-2.08; p = .015) in patients with G12C mutation than in those with non-G12C mutations. Furthermore, multivariate analysis showed that KRAS G12C mutation was independently associated with shorter first-line PFS and OS. Thus, these findings underscore the relevance of a stratified treatment targeting KRAS G12C mutation in mCRC.


Asunto(s)
Neoplasias Colorrectales , Proteínas Proto-Oncogénicas p21(ras) , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/genética , Humanos , Mutación , Pronóstico , Proteínas Proto-Oncogénicas p21(ras)/genética , Estudios Retrospectivos
7.
Invest New Drugs ; 39(5): 1399-1404, 2021 10.
Artículo en Inglés | MEDLINE | ID: mdl-33835357

RESUMEN

Background Combination therapy of gemcitabine with cisplatin (GC) is a standard first-line therapy for unresectable or recurrent biliary tract cancer (BTC). S-1 is often used as a second-line therapy in clinical practice, based on the results of some clinical studies investigating its efficacy and safety following gemcitabine monotherapy. However, few studies have reported on the clinical outcomes of S-1 following GC. The purpose of this study was to elucidate the efficacy and safety of S-1 following GC for unresectable and recurrent BTC. Methods We retrospectively collected the data of 116 patients (pts) who were treated with S-1 as a second-line therapy following GC for unresectable or recurrent BTC at Shizuoka Cancer Center (November 2009 to July 2019). Results Of these 116 pts., 84 were assessable. Patient characteristics were as follows: intrahepatic bile duct/extrahepatic bile duct/gallbladder cancer, 30/23/31 pts.; metastatic/recurrent/locally advanced, 57/17/10 pts. The median time to treatment failure and overall survival were 2.5 and 6.0 months, respectively. Among 65 pts. with measurable lesions, the overall response rate was 3.1% (2/65 pts) and the disease control rate was 24.6% (19/65 pts). The common grade 3/4 toxicities included anemia (12%), neutropenia (4%), infections (16%), fatigue (6%), and diarrhea (4%). Dose reduction or treatment schedule modification of S-1 was required in 29 pts. (34.5%), and 17 pts. (20%) terminated S-1 due to adverse events. Conclusions The efficacy and safety of S-1 following GC were almost the same as those of S-1 following GEM monotherapy for unresectable or recurrent BTC.


Asunto(s)
Antineoplásicos/uso terapéutico , Neoplasias del Sistema Biliar/tratamiento farmacológico , Cisplatino/uso terapéutico , Desoxicitidina/análogos & derivados , Ácido Oxónico/uso terapéutico , Tegafur/uso terapéutico , Adulto , Anciano , Antineoplásicos/administración & dosificación , Antineoplásicos/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias del Sistema Biliar/mortalidad , Neoplasias del Sistema Biliar/patología , Cisplatino/administración & dosificación , Cisplatino/efectos adversos , Desoxicitidina/administración & dosificación , Desoxicitidina/efectos adversos , Desoxicitidina/uso terapéutico , Combinación de Medicamentos , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Recurrencia Local de Neoplasia , Ácido Oxónico/administración & dosificación , Ácido Oxónico/efectos adversos , Estudios Retrospectivos , Tegafur/administración & dosificación , Tegafur/efectos adversos , Gemcitabina
8.
Int J Clin Oncol ; 26(10): 1822-1830, 2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-34152533

RESUMEN

BACKGROUND: Distant metastasis is a poor prognostic factor in recurrent/metastatic squamous cell carcinoma of the head and neck. However, limited information on the prognostic impact of locoregional disease is available, despite its life-threatening features. We investigated the prognostic impact of incurable locoregional disease and distant metastasis in recurrent/metastatic squamous cell carcinoma of the head and neck. METHODS: We retrospectively analyzed 156 patients with recurrent/metastatic squamous cell carcinoma of the head and neck who received palliative chemotherapy between August 2006 and December 2019. RESULTS: The median follow-up time for all censored patients was 12.1 (range 1.9-63.5) months. The median overall survival was 12.4 (95% confidence interval 10.1-15.1) months. Incurable locoregional disease (hazard ratio: 2.31, P = 0.007), liver metastasis (hazard ratio: 2.84, P = 0.006), disease-free interval > 13 months (hazard ratio: 0.51, P = 0.041), cetuximab use (hazard ratio: 0.59, P = 0.007), and immune checkpoint inhibitor use (hazard ratio: 0.56, P = 0.006) were associated with prognosis. The number of distant metastatic sites was not associated with overall survival (1-2: hazard ratio: 0.60, P = 0.16; 3-4: hazard ratio: 1.34, P = 0.50). Patients with incurable locoregional disease had more life-threatening events than those with curable locoregional disease. CONCLUSION: The presence of incurable locoregional disease had a significant prognostic impact, whereas the number of distant metastatic sites had no prognostic impact. Liver metastasis was a poor prognostic factor for recurrent/metastatic squamous cell carcinoma of the head and neck.


Asunto(s)
Neoplasias de Cabeza y Cuello , Neoplasias de Cabeza y Cuello/tratamiento farmacológico , Humanos , Recurrencia Local de Neoplasia , Pronóstico , Estudios Retrospectivos , Carcinoma de Células Escamosas de Cabeza y Cuello/tratamiento farmacológico
9.
Int J Clin Oncol ; 26(11): 2025-2028, 2021 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-34476649

RESUMEN

BACKGROUND: An infusion-related reaction (IRR) is a well-known adverse event related to monoclonal antibodies, and antihistamine premedication is recommended to prevent IRRs. Ramucirumab plus FOLFIRI therapy is the standard second-line treatment for metastatic colorectal cancer (CRC). Ramucirumab is a fully human antibody, suggesting that the incidence of IRRs is lower, however, the current recommendation for the proper use of ramucirumab is antihistamine premedication, but the incidence and severity of ramucirumab-induced IRR without antihistamine premedication have not been elucidated. METHODS: A retrospective study to evaluate the incidence of ramucirumab-induced IRRs in unresectable CRC patients treated by ramucirumab plus FOLFIRI therapy. If the incidence of IRR without antihistamine premedication was not higher than that of cetuximab in a previous report (5.7%), planning a prospective study was considered. RESULTS: A total of 147 patients with unresectable CRC who had been treated by ramucirumab plus FOLFIRI therapy were identified. Of them, 106 (72%) patients received intravenous antihistamine premedication. An IRR occurred in 2 patients (1.4%), 1 grade 2 and 1 grade 3. They received antihistamine and steroid premedication. On the other hand, IRRs were not observed in 41 patients without antihistamine premedication, and the incidence of IRRs was significantly lower compared with the previous report of cetuximab (p < 0.001). CONCLUSION: The incidence of ramucirumab-induced IRRs without antihistamine premedication is low. Not using antihistamine premedication can decrease medical costs. These findings warrant further investigation in large-scale cohorts to clarify the incidence and severity of ramucirumab-induced IRRs and further clarify the proper use of ramucirumab.


Asunto(s)
Anticuerpos Monoclonales Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Colorrectales , Anticuerpos Monoclonales Humanizados/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias Colorrectales/tratamiento farmacológico , Humanos , Estudios Prospectivos , Estudios Retrospectivos , Ramucirumab
10.
Int J Clin Oncol ; 26(6): 1039-1048, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-33683512

RESUMEN

BACKGROUND: De-escalating treatments have been focused on for HPV-associated oropharyngeal squamous cell carcinoma (OPSCC). We assessed the efficacy of a triplet induction chemotherapy (ICT) followed by surgery with or without neck dissection (ND) for locally advanced OPSCC, aiming at less invasive surgery without free-flap reconstruction and avoiding postoperative irradiation. METHODS: This was a retrospective study of 41 patients with advanced resectable HPV-positive OPSCC who underwent ICT followed by surgery of primary resection with or without ND. Patients underwent triplet ICT, including docetaxel, cisplatin, and 5-fluorouracil, or carboplatin, paclitaxel, and cetuximab. RESULTS: Twenty-nine patients had tonsillar cancer, 15 patients were current smokers, and 18 and 12 patients had T2N1M0 and T1N1M0 status (UICC 8th), respectively. After ICT, a surgical procedure without free-flap reconstruction and tracheostomy was possible in 90.2%. Pathological complete response at both the primary site and lymph nodes was achieved in 73.2%. Of the patients who underwent surgery, no adjuvant radiotherapy was required in 85.0%. Two patients (4.9%) experienced recurrence at regional lymph nodes, but were cured by salvage ND followed by adjuvant radiotherapy. CONCLUSIONS: Upfront ICT using highly responsive triplet chemotherapeutic regimens may enable us to perform less invasive surgery without free-flap reconstruction and to avoid postoperative irradiation to the locoregional field through excellent postoperative pathological features.

11.
BMC Cancer ; 20(1): 182, 2020 Mar 04.
Artículo en Inglés | MEDLINE | ID: mdl-32131771

RESUMEN

BACKGROUND: Aspiration pneumonia is one of the most important side effects of chemoradiotherapy (CRT) and bio-radiotherapy (BRT) in patients with head and neck cancer (HNC). Aspiration pneumonia can lead to cancer-related mortality in HNC patients. However, the relationship between aspiration pneumonia occurring during CRT or BRT for HNC and treatment outcomes in HNC patients is not well characterized. In this study, we assessed the influence of aspiration pneumonia on treatment outcomes and sought to identify the clinical risk factors for aspiration pneumonia during definitive CRT and BRT in HNC patients. METHODS: We retrospectively assessed the data pertaining to patients with locally advanced HNC who received definitive CRT or BRT at the Shizuoka Cancer Center between August 2006 and December 2016. RESULTS: Among the 374 HNC patients who received CRT or BRT, 95 (25.4%) developed aspiration pneumonia during treatment. Aspiration pneumonia was significantly associated with therapeutic response to CRT or BRT (multivariate adjusted odds ratio for complete response, 0.52, p = 0.020) and poor overall survival (multivariate adjusted hazard ratio for overall survival, 1.58, p = 0.024). The multivariate analyses identified four independent factors for aspiration pneumonia: poor oral hygiene, high N-classification, hypoalbuminemia before treatment, and inpatient treatment. CONCLUSIONS: Aspiration pneumonia occurring during CRT or BRT has a detrimental effect on the therapeutic response and survival of HNC patients. Careful attention should be paid to these risk factors for aspiration pneumonia in HNC patients undergoing CRT or BRT.


Asunto(s)
Quimioradioterapia/efectos adversos , Neoplasias de Cabeza y Cuello/terapia , Neumonía por Aspiración/epidemiología , Radioterapia/efectos adversos , Rituximab/efectos adversos , Femenino , Neoplasias de Cabeza y Cuello/patología , Humanos , Incidencia , Masculino , Estadificación de Neoplasias , Neumonía por Aspiración/inducido químicamente , Radioterapia/métodos , Estudios Retrospectivos , Factores de Riesgo , Rituximab/uso terapéutico , Análisis de Supervivencia , Resultado del Tratamiento
12.
Curr Oncol Rep ; 22(12): 118, 2020 09 18.
Artículo en Inglés | MEDLINE | ID: mdl-32945988

RESUMEN

PURPOSE OF REVIEW: Cisplatin has been established as one of the most important agents in multidisciplinary treatment for head and neck cancer (HNC). However, since HNC patients are often elderly and typically have several comorbidities, a limited number of patients can tolerate high-dose cisplatin in real-world HNC populations. We will provide a review of therapeutic alternatives to high-dose cisplatin-based treatment in the setting of definitive and postoperative chemoradiotherapy (CRT) or induction chemotherapy. RECENT FINDINGS: Clinical criteria for CDDP ineligibility have been discussed in HNC. When considering cisplatin-based chemotherapy as part of a non-surgical approach, precise evaluation of the patient's physical condition, nutritional status, and comorbidities is needed. Upfront surgery is an important option with high curability, if a de-intensified non-surgical approach is estimated to be unavoidable. Although no prospective data are available regarding alternatives to definitive cisplatin-based combination therapy for patients undergoing a non-surgical approach, cetuximab, carboplatin, or split-dose cisplatin-based regimens may be employed for cisplatin-ineligible patients in clinical practice. The combination of immune checkpoint inhibitors with radiotherapy may be a promising novel approach, and some trials are currently targeting the specific cohort of patients ineligible for high-dose cisplatin. There are no standard treatments for patients ineligible for high-dose cisplatin. A personalized treatment strategy should be proposed based on the individual benefit-to-risk ratio of each treatment option in patients ineligible for the standard of care. Prospective clinical trials for cisplatin-ineligible patients with locally advanced HNC still need to be performed.


Asunto(s)
Quimioradioterapia , Neoplasias de Cabeza y Cuello/terapia , Quimioterapia de Inducción , Carcinoma de Células Escamosas de Cabeza y Cuello/terapia , Anciano , Carboplatino/uso terapéutico , Cetuximab/uso terapéutico , Cisplatino/uso terapéutico , Ensayos Clínicos como Asunto , Neoplasias de Cabeza y Cuello/cirugía , Humanos , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Carcinoma de Células Escamosas de Cabeza y Cuello/cirugía
13.
Int J Clin Oncol ; 25(11): 1914-1920, 2020 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-32648132

RESUMEN

BACKGROUND: Docetaxel, cisplatin, and 5-fluorouracil (TPF) induction chemotherapy (ICT) is a treatment option for locally advanced unresectable head and neck squamous cell carcinoma (LA-HNSCC). However, patients with advanced age, or renal, cardiac or neurogenic dysfunction are ineligible for ICT-TPF. METHODS: We retrospectively assessed 24 unresectable LA-HNSCC patients who received paclitaxel, carboplatin and cetuximab (PCE) as ICT at the Shizuoka Cancer Center between April 2013 and October 2018. RESULTS: Patient characteristics were as follows: median age, 72 years (range 60-81); 0, 1, and 2 performance status (PS), 1, 15, and 8 patients, respectively, and creatinine clearance ≥ 60 mL/min or < 60 mL/min, 8 and 16 patients, respectively. The main reasons for PCE selection were renal impairment, older age, cardiac dysfunction, poor PS, and cerebral infarction. Twenty-two patients (92%) completed two or three cycles of ICT-PCE. After ICT-PCE, one patient (4%) and 20 patients (83%) achieved a complete response and partial response, respectively. Twenty-one patients (87%) advanced to definitive locoregional treatment. Median observation period was 25.2 months. The 12-month progression-free and overall survival rates were 75 and 92%, respectively. Median progression-free survival and overall survival were 29.4 and 34.8 months, respectively. Grade 3 or 4 toxicities included neutropenia (58%), oral mucositis (8%), and febrile neutropenia (4%). CONCLUSIONS: ICT-PCE may be a tolerable and potential option for unresectable LA-HNSCC patients ineligible for TPF.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de Cabeza y Cuello/tratamiento farmacológico , Carcinoma de Células Escamosas de Cabeza y Cuello/tratamiento farmacológico , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Carboplatino/administración & dosificación , Cetuximab/administración & dosificación , Cisplatino/administración & dosificación , Docetaxel/administración & dosificación , Estudios de Factibilidad , Femenino , Fluorouracilo/administración & dosificación , Neoplasias de Cabeza y Cuello/mortalidad , Humanos , Quimioterapia de Inducción , Masculino , Persona de Mediana Edad , Paclitaxel/administración & dosificación , Estudios Retrospectivos , Carcinoma de Células Escamosas de Cabeza y Cuello/mortalidad , Carcinoma de Células Escamosas de Cabeza y Cuello/cirugía , Resultado del Tratamiento
14.
Cancer Sci ; 110(2): 707-716, 2019 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-30447099

RESUMEN

Studies have indicated an association between UDP-glucuronosyltransferase-1A1 (UGT1A1) genetic polymorphisms and irinotecan-induced toxicity. We undertook this study to investigate the association between UGT1A1 genetic polymorphisms and toxicity in patients treated with the FOLFIRINOX (comprising oxaliplatin, irinotecan, fluorouracil, and leucovorin) chemotherapy regimen in the JASPAC 06 study. Patients screened for UGT1A1*6 and UGT1A1*28, and treated with either the original FOLFIRINOX (oxaliplatin 85 mg/m2 , irinotecan 180 mg/m2 , leucovorin 200 mg/m2 , bolus 5-fluorouracil [5-FU] 400 mg/m2 , and continuous 5-FU 2400 mg/m2 ) or a modified FOLFIRINOX (oxaliplatin 85 mg/m2 , irinotecan 150 mg/m2 , leucovorin 200 mg/m2 , and continuous 5-FU 2400 mg/m2 ) as first-line chemotherapy were included. Of 199 patients eligible for this analysis, 79 patients were treated with the original FOLFIRINOX regimen and 120 patients were treated with the modified FOLFIRINOX regimen. In the original FOLFIRINOX group, 54 were UGT1A1 WT, and 25 were UGT1A1 heterozygous type (-/*6, 12 patients; -/*28, 13 patients). In the modified FOLFIRINOX group, 64 were UGT1A1 WT and 56 were UGT1A1 heterozygous type (-/*6, 33 patients; -/*28, 23 patients). In the original FOLFIRINOX group, the incidence of diarrhea was significantly higher among patients with UGT1A1 heterozygous type than among those with UGT1A1 WT and the incidence of leukopenia and diarrhea was significantly higher among patients with UGT1A1 -/*6 than among those with UGT1A1 -/*28. Patients with UGT1A1 heterozygous type, especially those with UGT1A1 -/*6, tended to show a higher incidence rate of severe adverse events, but this was not statistically significant. However, for patients who received the modified FOLFIRINOX, there was no difference in the frequency of adverse events due to UGT1A1 status. In conclusion, patients with heterozygous UGT1A1 polymorphisms treated with the original FOLFIRINOX regimen experienced severe toxicity more frequently than patients with WT UGT1A1.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Fluorouracilo/uso terapéutico , Glucuronosiltransferasa/genética , Leucovorina/uso terapéutico , Compuestos Organometálicos/uso terapéutico , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/genética , Polimorfismo Genético/genética , Adulto , Anciano , Combinación de Medicamentos , Femenino , Heterocigoto , Humanos , Irinotecán/farmacología , Masculino , Persona de Mediana Edad , Oxaliplatino
15.
Tumour Biol ; 40(2): 1010428318760420, 2018 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-29463190

RESUMEN

CYFRA 21-1 is a prognostic marker for non-small cell lung cancer. The serum CYFRA 21-1 level is also known as an adjunct for the diagnosis of lung squamous cell carcinoma. This study aimed to examine whether CYFRA 21-1 has predictive implications for nivolumab therapy in patients with advanced lung adenocarcinoma. Of the 79 patients who were treated with nivolumab therapy at the Shizuoka Cancer Center between December 2015 and September 2016, we retrospectively reviewed the data of 50 patients. The patient characteristics were as follows: age <70/≥70 years: 43 (86%)/7; male/female: 31 (62.0%)/19; Eastern Cooperative Oncology Group performance status 0-1/2: 43 (86%)/7; smoking status: no/yes: 18 (36%)/32; epidermal growth factor receptor mutation status negative/positive: 36 (72%)/14; CYFRA 21-1 ≥2.2/<2.2 ng/mL: 28 (56%)/22; carcinoembryonic antigen ≥5/<5 ng/mL: 29 (58%)/21; and number of prior regimens 2-3/≥4: 16 (32%)/34. With a median follow-up of 263.5 (range, 64-352) days, the median progression-free survival was 70 days. The clinical variables investigated using univariate analysis were as follows: age (p = 0.423), carcinoembryonic antigen (p = 0.888), epidermal growth factor receptor mutation status (p = 0.105), performance status (p = 0.968), sex (p = 0.210), number of prior regimens (p = 0.146), CYFRA 21-1 (p = 0.026), and smoking status (p = 0.041). A multivariate analysis identified a serum CYFRA 21-1 level ≥2.2 ng/mL as an independent predictor of a favorable outcome (hazard ratio, 0.44; 95% confidence interval, 0.23-0.85; p = 0.015; median progression-free survival, 155 vs 51.5 days). In conclusion, CYFRA 21-1 might be an independent predictor of outcome for patients with advanced lung adenocarcinoma treated with nivolumab.


Asunto(s)
Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/metabolismo , Anticuerpos Monoclonales/uso terapéutico , Antígenos de Neoplasias/metabolismo , Queratina-19/metabolismo , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/metabolismo , Adenocarcinoma del Pulmón , Adulto , Anciano , Biomarcadores de Tumor/metabolismo , Antígeno Carcinoembrionario/metabolismo , Supervivencia sin Enfermedad , Receptores ErbB/metabolismo , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Nivolumab , Estudios Retrospectivos
16.
BMC Cancer ; 18(1): 573, 2018 May 18.
Artículo en Inglés | MEDLINE | ID: mdl-29776344

RESUMEN

BACKGROUND: Standard treatment for unresectable esophageal squamous cell carcinoma (ESCC) without distant metastasis is definitive chemoradiotherapy (dCRT), in which the incidence of esophageal fistula (EF) is reported to be 10-12%. An ad hoc analysis of JCOG0303, a phase II/III trial of dCRT for patients with unresectable ESCC (including non-T4b), suggested that esophageal stenosis is a risk factor for EF. However, risk factors for EF in patients limited to T4b ESCC treated with dCRT have yet to be clarified. The aim of this study was to investigate risk factors for EF in T4b thoracic ESCC treated with dCRT. METHODS: We retrospectively analyzed the data of consecutive T4b thoracic ESCC patients who were treated with dCRT (cisplatin and fluorouracil) at Shizuoka Cancer Center between April 2004 and September 2015. RESULTS: Excluding 8 patients with esophageal fistula clearly attributable to other iatrogenic interventions, the data of 116 patients who met the inclusion criteria were analyzed. Esophageal fistula was observed in 28 patients (24%). Although the fistula was closed in 5 patients, overall survival was significantly shorter in patients who experienced esophageal fistula (8.0 vs. 26.8 months; p < 0.0001). Among four potential variables extracted in univariate analysis, namely, total circumferential lesion, elevated CRP level, elevated white blood cell count, and anemia, the first two were revealed as risk factors for esophageal fistula in multivariate analysis. CONCLUSIONS: This study demonstrated that total circumferential lesion and CRP ≥1.00 mg/dL are risk factors for esophageal fistula in T4b thoracic ESCC treated with dCRT. TRIAL REGISTRATION: This study was retrospectively registered.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Fístula Esofágica/epidemiología , Neoplasias Esofágicas/patología , Carcinoma de Células Escamosas de Esófago/patología , Adulto , Anciano , Proteína C-Reactiva/análisis , Estudios de Casos y Controles , Quimioradioterapia/métodos , Cisplatino/uso terapéutico , Fístula Esofágica/sangre , Fístula Esofágica/etiología , Neoplasias Esofágicas/sangre , Neoplasias Esofágicas/complicaciones , Neoplasias Esofágicas/terapia , Carcinoma de Células Escamosas de Esófago/sangre , Carcinoma de Células Escamosas de Esófago/complicaciones , Carcinoma de Células Escamosas de Esófago/terapia , Femenino , Fluorouracilo/uso terapéutico , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Pronóstico , Estudios Retrospectivos , Factores de Riesgo
17.
Gastric Cancer ; 21(2): 338-344, 2018 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-28577228

RESUMEN

BACKGROUND: Several studies have demonstrated the benefit of hepatectomy for treating gastric cancer (GC) with liver-limited metastases (LLM). The survival benefit of hepatectomy compared with that of systemic chemotherapy is unknown, particularly in patients with multiple LLM. This study investigated the survival benefit of hepatectomy compared with that of systemic chemotherapy administered to patients with GC with multiple LLM. METHODS: We retrospectively reviewed the data of consecutive patients with GC with two or three LLM who underwent hepatectomy or received systemic chemotherapy as initial treatment at the Shizuoka Cancer Center between December 2004 and December 2015. RESULTS: Nine of 24 patients who met the inclusion criteria underwent hepatectomy, and 15 received chemotherapy. In the hepatectomy group, all patients achieved R0 resection and none died during hospitalization. Three patients received adjuvant chemotherapy. Disease recurred in eight patients (88.9%). In the chemotherapy group, three patients underwent hepatectomy following initial chemotherapy and did not experience recurrence or death during follow-up. Median follow-up was 47.9 months and median overall survival (OS) was 38.1 and 24.8 months in the chemotherapy and hepatectomy groups, respectively. Multivariate analysis of OS, including initial treatment, revealed that unilobar liver metastasis was the only independent favorable prognostic factor. CONCLUSIONS: Although hepatectomy for patients with GC with multiple LLM is not recommended as the initial therapy, it prolonged the survival of patients with tumors controlled using systemic chemotherapy.


Asunto(s)
Adenocarcinoma/secundario , Adenocarcinoma/cirugía , Neoplasias Hepáticas/secundario , Neoplasias Hepáticas/cirugía , Neoplasias Gástricas/patología , Adenocarcinoma/tratamiento farmacológico , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Quimioterapia Adyuvante , Supervivencia sin Enfermedad , Femenino , Hepatectomía/mortalidad , Humanos , Estimación de Kaplan-Meier , Neoplasias Hepáticas/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/cirugía
18.
Nihon Rinsho ; 74(11): 1852-1856, 2016 11.
Artículo en Japonés | MEDLINE | ID: mdl-30550694

RESUMEN

In the last decade unprecedented advances have been seen in the treatment of metastatic colorectal cancer(mCRC). Clinical developments of many active agents have contributed to this great progress in the prognosis of mCRC. Recently, new active agents and combination chemotherapies have been developed and reported promising results for HER2 positive, BRAF mutant, and MSI-High mCRC patients. On the other hand, IDEA project is on-going for patients with stage II colon cancer, to answer whether a three-month course of oxaliplatin. -based adjuvant therapy (FOLFOX4/modified FOLFOX6 or XELOX) is non-inferior to the current standard six-month treatment. This chapter focuses on the current status and the future Dersoective of chemotherapy for colorectal cancer.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológico , Humanos
19.
Nat Med ; 29(1): 127-134, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36646802

RESUMEN

Despite standard-of-care treatment, more than 30% of patients with resectable colorectal cancer (CRC) relapse. Circulating tumor DNA (ctDNA) analysis may enable postsurgical risk stratification and adjuvant chemotherapy (ACT) treatment decision-making. We report results from GALAXY, which is an observational arm of the ongoing CIRCULATE-Japan study (UMIN000039205) that analyzed presurgical and postsurgical ctDNA in patients with stage II-IV resectable CRC (n = 1,039). In this cohort, with a median follow-up of 16.74 months (range 0.49-24.83 months), postsurgical ctDNA positivity (at 4 weeks after surgery) was associated with higher recurrence risk (hazard ratio (HR) 10.0, P < 0.0001) and was the most significant prognostic factor associated with recurrence risk in patients with stage II or III CRC (HR 10.82, P < 0.001). Furthermore, postsurgical ctDNA positivity identified patients with stage II or III CRC who derived benefit from ACT (HR 6.59, P < 0.0001). The results of our study, a large and comprehensive prospective analysis of ctDNA in resectable CRC, support the use of ctDNA testing to identify patients who are at increased risk of recurrence and are likely to benefit from ACT.


Asunto(s)
Neoplasias Colorrectales , Recurrencia Local de Neoplasia , Humanos , Recurrencia Local de Neoplasia/patología , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Quimioterapia Adyuvante , Modelos de Riesgos Proporcionales , Japón , Biomarcadores de Tumor/genética , Neoplasia Residual/tratamiento farmacológico
20.
Cancer Med ; 11(11): 2184-2192, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-35182029

RESUMEN

BACKGROUND: The development of chemotherapy and treatment strategies for metastatic colorectal cancer (mCRC) have provided patients with significant survival benefits. Currently, molecular targeting agents and late-line treatment with regorafenib and trifluridine/tipiracil (FTD/TPI) are available. However, the impact of this increase in drug availability on overall survival (OS) in mCRC remains a clinical question. METHODS: We retrospectively collected data on consecutive mCRC patients who were treated at three institutions in Japan. We divided the patients into three cohorts: patients who initiated first-line treatment from Jan 2005 to Dec 2006 (cohort A: only cytotoxic drugs available), Jan 2007 to Dec 2011 (cohort B: molecular targeting drugs available), and Jan 2012 to Sep 2016 (cohort C: late-line treatment available). RESULTS: A total of 1409 consecutive patients were analyzed. The median survival time (MST) in cohorts A, B, and C was 18.6, 25.4, and 26.4 months, respectively. The hazard ratio (HR) for cohort B versus A was 0.81 (95% CI 0.68-0.97), for cohort C versus A was 0.74 (95% CI 0.61-0.89), and for cohort C versus B was 0.92 (0.81-1.03). The median number of administered drugs (range) was 3 (1-5) in cohort A, 4 (1-7) in cohort B, and 4 (1-7) in cohort C. The increase in drug availability extended the MST from 15.5 months in patients treated with ≤3 drugs to 36.0-37.3 months in patients treated with six to seven drugs. CONCLUSION: The development of chemotherapy including late-line treatments could improve the prognosis of mCRC patients.


Asunto(s)
Neoplasias del Colon , Neoplasias Colorrectales , Neoplasias del Recto , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias del Colon/tratamiento farmacológico , Neoplasias Colorrectales/patología , Combinación de Medicamentos , Humanos , Pronóstico , Neoplasias del Recto/tratamiento farmacológico , Estudios Retrospectivos
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